The present invention relates to medically useful radioisotopes, and particularly to no-carrier-added (NCA) radioisotopes of tin and methods of preparing NCA radioisotopes of tin.
The use of beta particle-emitting radioisotopes for applications in nuclear medicine, oncology and interventional cardiology is rapidly increasing because of the availability of new pharmaceutical targeting approaches, which effectively concentrate or localize the radioactive vector at the target site with low uptake in non-target tissues. In this manner, the energy released from decay of the radioisotope can be localized for killing cells at the target site, such as the cells of a tumor. In this regard, the use of such radiopharmaceuticals has been shown to be effective in treating a variety of tumors and cancers.
Approximately 320,000 new cases of bone cancer are reported annually in the United States. A complex of 117mSn (Sn4+) chelated to dietheylenetriamine pentaacetic acid (DTPA) has been used in clinical trials as a bone seeking pain reliever for metastatic bone cancers which are currently untreatable and fatal. The 117mSn complex does not sedate the patient, as do narcotic drugs, and provides selective radiation to the metastatic bone tumor while providing little radiation to the bone marrow. Consequently, the 117mSn complex does not interfere with the bone marrow's ability to fight infection and does not interfere with blood clotting.
The nuclear-physical and biochemical properties of 117mSn have enabled its useful application in nuclear medicine. The radioisotope 117mSn possesses a relatively short 14-day half-life, a gamma emission of 158 keV (87%) and a high yield of short-range conversion electrons with energies of 126 keV (64%), 152 keV (26%) and 129 keV(11%).
The effectiveness of a radioisotope that emits particles, such as beta particles, can be improved if the specific activity of a radioisotope construct is increased and if a construct can be designed to specifically target a site of interest. However, specific activity is often limited by the available production methods for the isotope and the subsequent purification procedure. Therefore, a recognized need exists in the art for medically useful radionuclides with high specific activities that are targetable and have little or no effect on healthy tissue or organs.
A common method for the production of the radioisotope 117mSn is through a “direct” method in a nuclear reactor via thermal neutron capture [116Sn(n,γ) 117mSn] or via non-elastic neutron scattering [117Sn(n,n′,γ) 117mSn] reactions. Because the nonradioactive target atoms and radioactive product atoms are not chemically separable, the radioactive 117mSn is diluted with significant amounts of the target isotope of tin. This excess of non-radioactive tin atoms therefore acts like a carrier, which inherently reduces the specific activity of the sample. With 97% or greater enriched-117Sn as a target, maximum specific activities of up to about 20 to about 23 Ci/g have been achieved using thermal neutrons, [117Sn (n, n′γ) 117mSn]. This is substantially less than the theoretically possible specific activity of about 82,000 Ci/g, thereby leaving much room for improvement. In addition, the much longer-lived 113Sn isotope may be produced from the thermal neutron “direct” method with the naturally-occurring 112Sn isotopic impurity. The radioactive 113Sn isotope has a half-life of 115 days and two higher energy gamma rays of 392 keV (64%) and 255 keV (2%). The radioisotope 113Sn is generally considered harmful for nuclear medicine applications, because of the potential for extended patient exposure to radiation.
Conversely, there are several known methods of producing NCA 117mSn. For example, reactions utilizing non-tin target atoms may employ proton-induced, 3He-particle-induced, or α-particle-induced reactions on cadmium and indium targets. Many reactions, such as 114Cd(3He, γ), 114Cd(α,n), 116Cd(3He, 2n), 116Cd(α,3n), 115In(d, γ), 115In(3 He, p), and 115In(α, pn), are known to lead to the formation of NCA 117mSn, but are generally accompanied by production of some amount of the 113Sn radioisotope and other by-products.
Moreover, in addition to the manner of radioisotope generation, another major hindrance with producing NCA 117mSn with high specific activity is the absence of an effective method for separating 117mSn from the target material. Efficiently separating small quantities of a desired species from a much larger matrix, i.e. debulking, is notoriously difficult using conventional separation methods, such as chromatography or extraction. Historically, this very aspect of radionuclide purification provoked the use of a carrier, thereby rendering samples with reduced specific activity because of dilution by non-radioactive target atoms from the carrier.
Therefore, in view of the foregoing, a need exists for the production and isolation of NCA, high specific activity 117mSn acceptable for use in radiopharmaceuticals.